Search

Parathyroid hormone (PTH), which is elevated in patients with chronic renal failure, has been shown to participate in the development of vascular calcification. Previous studies have demonstrated that PTH may promote endothelial expressions of proinflammatory parameters. On the basis of these data, we evaluated whether PTH may have an impact on endothelial osteoprotegerin (OPG), a vascular-protective factor which may control vascular calcification. Endothelial cells were stimulated with [10.sup.-12] to [10.sup.-10] mol/l PTH. PKC and PKA are the main cellular pathways of PTH. Inhibitors and activators of PKC or PKA were used to determine whether these signaling pathways are involved in the control of endothelial OPG. PTH induced a decrease in OPG secretion and mRNA expression. Treatment of PTH-stimulated cells by calphostin C (PKC inhibitor) induced a further decrease in OPG secretion, while Rp-cAMP (PKA inhibitor) had no additional effect. In nonstimulated cells, a PKC activator significantly stimulated OPG secretion, while a PKA activator was associated with a decline. These effects were blunted in the presence of calphostin C and Rp-cAMP, respectively. An increase in OPG secretion induced by a PKC activator indicates that the basal OPG secretion is mediated through PKC. The decrease induced by a PKA activator, which is similar to the decrease observed with PTH, suggests that the action of PTH on OPG secretion and mRNA expression may be due to the PKA pathway. endothelial cells

Parathyroid hormone (PTH), which is elevated in patients with chronic renal failure, has been shown to participate in the development of vascular calcification. Previous studies have demonstrated that PTH may promote endothelial expressions of proinflammatory parameters. On the basis of these data, we evaluated whether PTH may have an impact on endothelial osteoprotegerin (OPG), a vascular-protective factor which may control vascular calcification. Endothelial cells were stimulated with 10-12 to 10-10 mol/l PTH. PKC and PKA are the main cellular pathways of PTH. Inhibitors and activators of PKC or PKA were used to determine whether these signaling pathways are involved in the control of endothelial OPG. PTH induced a decrease in OPG secretion and mRNA expression. Treatment of PTH-stimulated cells by calphostin C (PKC inhibitor) induced a further decrease in OPG secretion, while Rp-cAMP (PKA inhibitor) had no additional effect. In nonstimulated cells, a PKC activator significantly stimulated OPG secretion, while a PKA activator was associated with a decline. These effects were blunted in the presence of calphostin C and Rp-cAMP, respectively. An increase in OPG secretion induced by a PKC activator indicates that the basal OPG secretion is mediated through PKC. The decrease induced by a PKA activator, which is similar to the decrease observed with PTH, suggests that the action of PTH on OPG secretion and mRNA expression may be due to the PKA pathway. [ABSTRACT FROM AUTHOR]

Background: Acute renal infarction is an oft-missed diagnosis. As a result, its true incidence, although presumed to be low, is actually unknown. Surprisingly, the medical literature on the subject, other than anecdotal case reports, is scarce., Objectives: To increase physician awareness of the diagnosis and to identify predictive clinical and laboratory features of the entity., Method: Between 1 November 1997 and 31 October 2000, 11 cases of acute renal infarction in 10 patients were diagnosed in our center by contrast-enhanced computerized tomography. The medical charts of these patients were reviewed regarding risk factors, clinical presentation, possible predictive laboratory examinations, and outcome., Results: During the 36 month observation period, the incidence of acute renal infarction was 0.007%. The mean age of the patients (5 men and 5 women) was 67.4 +/- 21.1 (range 30-87 years). In four cases the right and in five the left kidney was involved; in the other two cases bilateral involvement was seen. In 7/10 patients, an increased risk for thromboembolic events was found. Six had chronic atrial fibrillation and one had a combined activated protein C resistance and protein S deficiency. Three patients had suffered a previous thromboembolic event. Two cases were receiving anticoagulant therapy with an INR of 1.6 and 1.8, respectively. On admission, flank pain was recorded in 10/11, fever in 5 and nausea/vomiting in 4 cases. Hematuria was detected in urine reagent strips in all cases. Serum lactate dehydrogenase and white blood cell count were elevated in all cases (1,570 +/- 703 IU/L and 12,988 +/- 3,841/microliter, respectively). In no case was the diagnosis of acute renal infarction initially entertained. The working diagnoses were renal colic in 2, pyelonephritis in 3, renal carcinoma, digitalis intoxication, and suspected endocarditis in one patient each, and an acute abdomen in 3. Time from admission to definitive CT diagnosis ranged from 24 hours to 6 days. Three patients were treated with intravenous heparin and another with a combination of i.v. heparin and renal intra-arterial urokinase infusion with, in the latter case, no recovery of function of the affected kidney. With the exception of this one patient (with a contralateral contracted kidney) who required maintenance dialysis, in all other cases serum creatinine levels remained unchanged or reverted to the baseline mean of 1.1 mg/dl (0.9-1.2)., Conclusions: Acute renal infarction is not as rare as previously assumed. The entity is often misdiagnosed. Unilateral flank pain in a patient with an increased risk for thromboembolism should raise the suspicion of renal infarction. In such a setting, hematuria, leucocytosis and an elevated LDH level are strongly supportive of the diagnosis.